Co-translational selenocysteine incorporation in algae

• Applicant: Dr. Tarek Hilal
• Subject Area: Structural Biology ; Biochemistry
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571438675

Selenocysteine (Sec), the 21st proteinogenic amino acid, is essential for the function of numerous proteins that play critical roles in redox regulation, embryonic development, and overall health. Selenoproteins are implicated in a variety of human diseases, including cancer, neurodegenerative disorders, and viral infections. While the mechanisms of Sec incorporation are well studied in bacteria and mammals, they remain poorly understood in algae-particularly in red algae, one of the oldest evolutionary lineages of photosynthetic eukaryotes. The unicellular red alga Cyanidioschyzon merolae (C. merolae) offers a unique model for investigating selenoprotein biology due to its compact genome, simple cellular structure, and adaptation to extreme environments such as acidic hot springs. This project aims to elucidate the molecular and structural mechanisms of Sec incorporation in C. merolae, providing fundamental insights into the evolution and adaptation of the selenoprotein synthesis machinery in algae. We will combine state-of-the-art cryogenic electron microscopy, in vitro translation assays, and advanced proteomics including cross-linking mass spectrometry to dissect the structural adaptations of the algal ribosome and its interaction with Sec-specific translation factors. Comparative analyses with mammalian and plant ribosomes will identify conserved and lineage-specific features that govern Sec incorporation and translational fidelity. The project is structured around three main objectives: (1) high-resolution structural and biochemical characterization of cytosolic ribosomes from C. merolae; (2) functional analysis of the Sec incorporation machinery, including the identification and characterization of key translation factors and SECIS elements; and (3) integrative proteomic studies to map the interactome and regulatory networks involved in selenoprotein synthesis. By leveraging unique local and international collaborations, including expertise in algal genetics and proteomics, this project will address a major gap in our understanding of selenoprotein biology in algae. The anticipated results will not only advance basic knowledge of genetic code expansion and translational regulation but may also inform biotechnological and biomedical applications, such as the engineering of stress-tolerant crops and the development of novel therapeutic strategies targeting selenoprotein pathways.

• DFG Programme: Research Grants